The coxsackievirus B3 (CVB3) strain Nancy P establishes a persistent carrier-state infection without visible cytopathic effect in primary human fibroblasts (HuFi H), whereas the derivative variant PD induces a complete lysis of the cell monolayer. To define the molecular basis of this exceptional growth property, the complete genomes of both viruses were sequenced and compared to all published sequences of CVB3. As a result, six unique amino acid substitutions in the VP1 capsid protein were observed. Via hybrid virus construction, the lytic phenotype was transferred to a nonlytic cDNA-generated CVB3. Mapping experiments indicate that the presence of amino acid residues K78, A80, A91, and I92 in VP1 is sufficient to induce "lytic" infections in HuFi H cells. Binding assays demonstrate that CVB3 Nancy P preferentially binds to the human coxsackievirus-adenovirus receptor (CAR), while PD exhibits a very weak interaction with CAR but strong binding to the decay accelerating factor (DAF). These results suggest that the mutated amino acid residues in VP1 are involved in receptor recognition/binding. Moreover, the lytic replication of CVB3 PD and the hybrid virus in various nonpermissive rodent cell lines indicates that cell surface molecules other than CAR and DAF may be involved in attachment of this variant to cell surfaces.
A new antibiotic complex has been isolated from cultures of Streptomyces strain No. JA 10124. On the basis of taxonomic studies, the producing microorganism is described as Streptomyces griseoflavus (KRAINSKY, 1914) WAKSMAN et HENRICI, 1948, subsp. thuringiensis subsp. nov., type strain JA 10124. The antibiotic complex, designated as streptovirudin, was isolated from extracts of both mycelium and culture filtrate. It is a white amorphous material which consists of ten closely related components including streptovirudins A, B, C, D and E. The streptovirudin complex exhibits antibiotic activity against Gram-positive bacteria, mycobacteria, and various DNA-and RNA-viruses. During the course of our screening program for antiviral antibiotics inhibition of various viruses was found with extracts from Streptomyces strain No. JA 10124. The organism was identified as a new subspecies of Streptomyces griseoflavus (KRAINSKY, 1914) WAKSMAN and HENRICI, 1948, for which the name Streptomyces griseoflavus subsp. thuringiensis is proposed. The name " streptovirudin " has been proposed for the antibiotic material isolated from fermentations of JA 10124.1,2) The antibiotic complex and each of its components appeared to be new and were therefore isolated in pure form. They are active against a variety of Gram-positive bacteria and various DNA-and RNA-viruses. The subject of this communication is the characterization of the producing strain, the fermentative production of the antibiotic complex, its isolation, purification and characterization.
Die Chinoxaline (II) und (III), die gegen DNS‐ und RNS‐Viren wirksam sind, werden aus den Diaminen (I) über die entsprech‐ enden Chinoxalinone durch Reaktion mit Phosphoroxychlorid erhalten.
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